Search

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+) through the amino acids, imparting advantageous mechanical properties like self‐healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self‐healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti‐inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above‐mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering. [ABSTRACT FROM AUTHOR]

Neuronal primary cilia are crucial for body weight maintenance. Type III adenylyl cyclase (AC3) is abundantly enriched in neuronal cilia, and mice with global AC3 ablation are obese. However, whether AC3 regulates body weight through its ciliary expression and the mechanism underlying this potential regulation are not clear. In this study, humanized AC3 knock‐in mice that are resistant to high‐fat diet (HFD)‐induced obesity are generated, and increases in the number and length of cilia in the ventromedial hypothalamus (VMH) are shown. It is demonstrated that mice with specifically knocked down ciliary AC3 expression in the VMH show pronounced HFD‐induced obesity. In addition, in vitro and in vivo analyses of the VMH show that ciliary AC3 regulates autophagy by binding an autophagy‐related gene, gamma‐aminobutyric acid A receptor‐associated protein (GABARAP). Mice with GABARAP knockdown in the VMH exhibit exacerbated HFD‐induced obesity. Overall, the findings may reveal a potential mechanism by which ciliary AC3 expression regulates body weight in the mouse VMH. [ABSTRACT FROM AUTHOR]

Catalytically inactive CRISPR‐Cas13 (dCas13)‐based base editors can achieve the conversion of adenine‐to‐inosine (A‐to‐I) or cytidine‐to‐uridine (C‐to‐U) at the RNA level, however, the large size of dCas13 protein limits its in vivo applications. Here, a compact and efficient RNA base editor (ceRBE) is reported with high in vivo editing efficiency. The larger dCas13 protein is replaced with a 199‐amino acid EcCas6e protein, derived from the Class 1 CRISPR family involved in pre‐crRNA processing, and conducted optimization for toxicity and editing efficiency. The ceRBE efficiently achieves both A‐to‐I and C‐to‐U base editing with low transcriptome off‐target in HEK293T cells. The efficient repair of the DMD Q1392X mutation (68.3±10.1%) is also demonstrated in a humanized mouse model of Duchenne muscular dystrophy (DMD) after AAV delivery, achieving restoration of expression for gene products. The study supports that the compact and efficient ceRBE has great potential for treating genetic diseases. [ABSTRACT FROM AUTHOR]

MXenes as an emerging two‐dimensional (2D) material have attracted tremendous interest in electrochemical energy‐storage systems such as supercapacitors. Nevertheless, 2D MXene flakes intrinsically tend to lie flat on the substrate when self‐assembling as electrodes, leading to the highly tortuous ion pathways orthogonal to the current collector and hindering ion accessibility. Herein, a facile strategy toward multi‐scale structural engineering is proposed to fabricate high‐performance MXene hydrogel supercapacitor electrodes. By unidirectional freezing of the MXene slurry followed by a designed thawing process in the sulfuric acid electrolyte, the hydrogel electrode is endowed with a three‐dimensional (3D) open macrostructure impregnated with sufficient electrolyte and H+‐intercalated microstructure, which provide abundant active sites for ion storage. Meanwhile, the ordered channels bring through‐electrode ion and electron transportation pathways that facilitate electrolyte infiltration and mass exchange between electrolyte and electrode. Furthermore, this strategy can also be extended to the fabrication of a 3D‐printed all‐MXene micro‐supercapacitor (MSC), delivering an ultrahigh areal capacitance of 2.0 F cm–2 at 1.2 mA cm–2 and retaining 1.2 F cm–2 at 60 mA cm–2 together with record‐high energy density (0.1 mWh cm–2 at 0.38 mW cm–2). [ABSTRACT FROM AUTHOR]

The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron‐based metal organic framework (Fe‐MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer‐specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non‐targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule‐associated protein 1A/1B‐light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy‐dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics. [ABSTRACT FROM AUTHOR]

Although activin receptor IIB (ACVR2B) is emerging as a novel pathogenic receptor, its ligand and assembled components (or assembly) are totally unknown in the context of osteoarthritis (OA) pathogenesis. The present results suggest that upregulation of ACVR2B and its assembly could affect osteoarthritic cartilage destruction. It is shown that the ACVR2B ligand, activin A, regulates catabolic factor expression through ACVR2B in OA development. Activin A Tg mice (Col2a1‐Inhba) exhibit enhanced cartilage destruction, whereas heterozygous activin A KO mice (Inhba+/−) show protection from cartilage destruction. In silico analysis suggests that the Activin A‐ACVR2B axis is involved in Nox4‐dependent ROS production. Activin A Tg:Nox4 KO (Col2a1‐Inhba:Nox4−/−) mice show inhibition of experimental OA pathogenesis. NOX4 directly binds to the C‐terminal binding site on ACVR2B‐ACVR1B and amplifies the pathogenic signal for cartilage destruction through SMAD2/3 signaling. Together, the findings reveal that the ACVR2B assembly, which comprises Activin A, ACVR2B, ACVR1B, Nox4, and AP‐1‐induced HIF‐2α, accelerates OA development. Furthermore, it is shown that shRNA‐mediated ACVR2B knockdown or trapping ligands of ACVR2B abrogate OA development by competitively disrupting the ACVR2B‐Activin A interaction. These results suggest that the ACVR2B assembly is required to amplify osteoarthritic cartilage destruction and could be a potential therapeutic target in efforts to treat OA. [ABSTRACT FROM AUTHOR]

Biopolymers are essential building blocks that constitute cells and tissues with well‐defined molecular structures and diverse biological functions. Their three‐dimensional (3D) complex architectures are used to analyze, control, and mimic various cells and their ensembles. However, the free‐form and high‐resolution structuring of various biopolymers remain challenging because their structural and rheological control depend critically on their polymeric types at the submicron scale. Here, direct 3D writing of intact biopolymers is demonstrated using a systemic combination of nanoscale confinement, evaporation, and solidification of a biopolymer‐containing solution. A femtoliter solution is confined in an ultra‐shallow liquid interface between a fine‐tuned nanopipette and a chosen substrate surface to achieve directional growth of biopolymer nanowires via solvent‐exclusive evaporation and concurrent solution supply. The evaporation‐dependent printing is biopolymer type‐independent, therefore, the 3D motor‐operated precise nanopipette positioning allows in situ printing of nucleic acids, polysaccharides, and proteins with submicron resolution. By controlling concentrations and molecular weights, several different biopolymers are reproducibly patterned with desired size and geometry, and their 3D architectures are biologically active in various solvents with no structural deformation. Notably, protein‐based nanowire patterns exhibit pin‐point localization of spatiotemporal biofunctions, including target recognition and catalytic peroxidation, indicating their application potential in organ‐on‐chips and micro‐tissue engineering. [ABSTRACT FROM AUTHOR]

Even though ZnO is commonly used as the ETL in the perovskite solar cell (PSC), the reactivity of perovskite deposited thereupon limits its performance. Herein, an ethylene diamine tetraacetic acid‐complexed ZnO (E‐ZnO) is successfully developed as a significantly improved electron selective layer (ESLs) in perovskite device. It is found that E‐ZnO exhibits higher electron mobility and better matched energy level with perovskite compared to ZnO. In addition, in order to eliminate the proton transfer reaction at the ZnO/perovskite interface, a high quality perovskite film fabrication process that requires neither annealing nor antisolvent is developed. By taking advantages of both E‐ZnO and the new process, the highest efficiency of 20.39% is obtained for PSCs based on E‐ZnO. Moreover, the efficiency of unencapsulated PSCs with E‐ZnO retains 95% of its initial value exposed in an ambient atmosphere after 3604 h. This work provides a feasible path toward high performance of PSCs, and it is believed that the present work will facilitate transition of perovskite photovoltaics in flexible and tandem devices since the annealing‐ and antisolvent‐free technology. [ABSTRACT FROM AUTHOR]

Even though ZnO is commonly used as the ETL in the perovskite solar cell (PSC), the reactivity of perovskite deposited thereupon limits its performance. Herein, an ethylene diamine tetraacetic acid‐complexed ZnO (E‐ZnO) is successfully developed as a significantly improved electron selective layer (ESLs) in perovskite device. It is found that E‐ZnO exhibits higher electron mobility and better matched energy level with perovskite compared to ZnO. In addition, in order to eliminate the proton transfer reaction at the ZnO/perovskite interface, a high quality perovskite film fabrication process that requires neither annealing nor antisolvent is developed. By taking advantages of both E‐ZnO and the new process, the highest efficiency of 20.39% is obtained for PSCs based on E‐ZnO. Moreover, the efficiency of unencapsulated PSCs with E‐ZnO retains 95% of its initial value exposed in an ambient atmosphere after 3604 h. This work provides a feasible path toward high performance of PSCs, and it is believed that the present work will facilitate transition of perovskite photovoltaics in flexible and tandem devices since the annealing‐ and antisolvent‐free technology. [ABSTRACT FROM AUTHOR]

As the power conversion efficiency (PCE) of perovskite solar cells (PSCs) is increased to as high over 25%, it becomes pre‐eminent to study a scalable process with wide processing window to fabricate large‐area uniform perovskite films with good light‐trapping performance. A stable and uniform intermediate‐state complex film is obtained by using tetramethylene sulfoxide (TMSO), which extends the annealing window to as long as 20 min, promotes the formation of a high‐quality perovskite film with larger grains (over 400 nm) and spontaneously forms the surface texture to result in an improved fill factor and open‐circuit voltage (Voc). Moreover, the superior surface texture significantly increases the long‐wavelength response, leading to an improved short‐circuit current density (Jsc). As a result, the maximum PCE of 21.14% is achieved based on a simple planar cell structure without any interface passivation. Moreover, a large area module with active area of 6.75 cm2 is assembled using the optimized TMSO process, showing efficiency as high as 16.57%. The study paves the way to the rational design of highly efficient PSCs for potential scaled‐up production. [ABSTRACT FROM AUTHOR]

Abstract: Organic–inorganic hybrid halide perovskites are proven to be a promising semiconductor material as the absorber layer of solar cells. However, the perovskite films always suffer from nonuniform coverage or high trap state density due to the polycrystalline characteristics, which degrade the photoelectric properties of thin films. Herein, the alkali metal ions which are stable against oxidation and reduction are used in the perovskite precursor solution to induce the process of crystallization and nucleation, then affect the properties of the perovskite film. It is found that the addition of the alkali metal ions clearly improves the quality of perovskite film: enlarges the grain sizes, reduces the defect state density, passivates the grain boundaries, increases the built‐in potential (Vbi), resulting to the enhancement in the power conversion efficiency of perovskite thin film solar cell. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second‐leading cause of cancer‐related mortality worldwide, which may be effectively reduced by early screening. Colon cancer secreted protein‐2 (CCSP‐2) is a promising blood marker for CRC. An electric‐field effect colorectal sensor (E‐FECS), an ion‐sensitive field‐effect transistor under dual gate operation with nanostructure is developed, to quantify CCSP‐2 directly from patient blood samples. The sensing performance of the E‐FECS is verified in 7 controls and 7 CRC samples, and it is clinically validated on 30 controls, 30 advanced adenomas, and 81 CRC cases. The concentration of CCSP‐2 is significantly higher in plasma samples from CRC and advanced adenoma compared with controls (both P < 0.001). Sensitivity and specificity for CRC versus controls are 44.4% and 86.7%, respectively (AUC of 0.67), and 43.3% and 86.7%, respectively, for advanced adenomas (AUC of 0.67). CCSP‐2 detects a greater number of CRC cases than carcinoembryonic antigen does (45.6% vs 24.1%), and the combination of the two markers detects an even greater number of cases (53.2%). The E‐FECS system successfully detects CCSP‐2 in a wide range of samples including early stage cancers and advanced adenoma. CCSP‐2 has potential for use as a blood‐based biomarker for CRC. [ABSTRACT FROM AUTHOR]

Up to now, multijunction cell design is the only successful way demonstrated to overcome the Shockley–Quiesser limit for single solar cells. Perovskite materials have been attracting ever‐increasing attention owing to their large absorption coefficient, tunable bandgap, low cost, and easy fabrication process. With their rapidly increased power conversion efficiency, organic–inorganic metal halide perovskite‐based solar cells have demonstrated themselves as the most promising candidates for next‐generation photovoltaic applications. In fact, it is a dream come true for researchers to finally find a perfect top‐cell candidate in tandem device design in commercially developed solar cells like single‐crystalline silicon and CIGS cells used as the bottom component cells. Here, the recent progress of multijunction solar cells is reviewed, including perovskite/silicon, perovskite/CIGS, perovskite/perovskite, and perovskite/polymer multijunction cells. In addition, some perspectives on using these solar cells in emerging markets such as in portable devices, Internet of Things, etc., as well as an outlook for perovskite‐based multijunction solar cells are discussed. Multijunction solar cells have demonstrated the capability to overcome the Shockley–Quiesser limit for sing‐junction solar cells. This work reviews the recent progress of the different types of multijunction solar cells based on perovskites, conceives a triple‐junction solar cell, and outlooks their applications in emerging markets such as in portable electrons, Internet of Things, etc. [ABSTRACT FROM AUTHOR]

Up to now, multijunction cell design is the only successful way demonstrated to overcome the Shockley–Quiesser limit for single solar cells. Perovskite materials have been attracting ever‐increasing attention owing to their large absorption coefficient, tunable bandgap, low cost, and easy fabrication process. With their rapidly increased power conversion efficiency, organic–inorganic metal halide perovskite‐based solar cells have demonstrated themselves as the most promising candidates for next‐generation photovoltaic applications. In fact, it is a dream come true for researchers to finally find a perfect top‐cell candidate in tandem device design in commercially developed solar cells like single‐crystalline silicon and CIGS cells used as the bottom component cells. Here, the recent progress of multijunction solar cells is reviewed, including perovskite/silicon, perovskite/CIGS, perovskite/perovskite, and perovskite/polymer multijunction cells. In addition, some perspectives on using these solar cells in emerging markets such as in portable devices, Internet of Things, etc., as well as an outlook for perovskite‐based multijunction solar cells are discussed. [ABSTRACT FROM AUTHOR]